There is now considerable evidence indicating that people who have a high need for novel and arousing stimulation (i.e., high sensation-seekers) use drugs more frequently than low sensation seekers. One interpretation of this relationship is that high sensation-seekers are predisposed biologically to find both novel stimuli and drugs to be more rewarding than low sensation-seekers. The major long-term objective of the present application is to determine if novelty-seeking and drug-seeking behaviors share a common overlapping mechanism in the brain. If these two behaviors are linked biologically, then perhaps novel stimulation may substitute for drug reward in high sensation-seekers. Using an animal model, rats will be evaluated for novelty-seeking behavior in three different behavioral measures: (1) activity in an inescapable novel compartment; (2) novelty-induced place preference; and (3) approach to a novel object. High and low novelty-seekers will then be evaluated for their behavioral response to amphetamine, cocaine and agonist drugs selective for either D1, D2, or D3 dopamine receptors. Parallel experiments will determine the functional activity of the mesolimbic dopamine system in both high and low novelty-seeking animals. Experiments will also be conducted to evaluate the role of environmental and genetic factors in determining novelty- and drug-seeking behaviors. The role of the environment will be examined by raising rats in one of three different conditions varying in stimulus novelty. They will then be examined for their response to drugs, as well as for differences in functional activity of the mesolimbic dopamine system. The role of genetics will be examined by screening a recombinant series of mouse strains for both novelty- and drug-seeking behaviors in order to determine if these behaviors are associated with common chromosomal loci in the mouse genome.